Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
J Biol Chem. 2012 Mar 30;287(14):11151-63. doi: 10.1074/jbc.M111.333922. Epub 2012 Feb 14.
Akt regulates a diverse array of cellular functions, including cell survival, proliferation, differentiation, and metabolism. Although a number of molecules have been identified as upstream regulators and downstream targets of Akt, the mechanisms by which Akt regulates these cellular processes remain elusive. Here, we demonstrate that a novel transcription factor, PHF20/TZP (referring to Tudor and zinc finger domain containing protein), binds to Akt and induces p53 expression at the transcription level. Knockdown of PHF20 significantly reduces p53. PHF20 inhibits cell growth, DNA synthesis, and cell survival. Akt phosphorylates PHF20 at Ser(291) in vitro and in vivo, which results in its translocation from the nucleus to the cytoplasm and attenuation of PHF20 function. These data indicate that PHF20 is a substrate of Akt and plays a role in Akt cell survival/growth signaling.
Akt 调节多种细胞功能，包括细胞存活、增殖、分化和代谢。虽然已经鉴定出许多分子作为 Akt 的上游调节剂和下游靶标，但 Akt 调节这些细胞过程的机制仍不清楚。在这里，我们证明了一种新的转录因子，PHF20/TZP（指含有 Tudor 和锌指结构域的蛋白），与 Akt 结合，并在转录水平诱导 p53 的表达。PHF20 的敲低显著降低了 p53 的表达。PHF20 抑制细胞生长、DNA 合成和细胞存活。Akt 在体外和体内将 PHF20 磷酸化于丝氨酸 291 位，导致其从核内易位到细胞质，并减弱 PHF20 的功能。这些数据表明 PHF20 是 Akt 的底物，在 Akt 细胞存活/生长信号转导中发挥作用。
